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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra m.rina capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo m.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and molecular medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2804-2818页

作者： Fenglian He Zhongen Wu Chenglong Liu Yuanyuan Zhu Yan Zhou Enming Tian rina Rosin-Arbesfeld Dehua Yang ming-Wei Wang Di Zhu Department of Pharmacology Minhang Hospitaland Key Laboratory of Smart Drug DeliveryShanghai Engineering Research Center of Immune TherapySchool of PharmacyFudan UniversityShanghai 201203China The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai 201203China Department of microbiology and Immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources SanyaChina Department of Chemistry School of ScienceThe University of TokyoTokyoJapan Engineering Research Center of Tropical medicine Innovation and Transformation of ministry of Education School of PharmacyHainan Medical UniversityHaikouChina Shandong Academy of Pharmaceutical Science JinanChina

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor *** B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against ***,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely ***,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into *** inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell ***,targeting BCL9/BCL9L promoted antigen presentation in *** is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 ***,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 ***,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor *** BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

关键词： immunity Targeting markedly

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激光散射特性的红外瞄准镜基线检测方法

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激光杂志 2024年第7期45卷 227-232页

作者：李波莎日娜内蒙古医科大学呼和浩特010110 中国人民解放军32302部队50分队北京101400

为提升武器射击精度,设计激光散射特性的红外瞄准镜基线检测方法。通过固定瞄准镜并利用黑体发射红外激光,在镜子反射后形成红外平行光束,并在瞄准镜视场内生成靶标的像。通过调整瞄准镜分划中心与靶标像中心重合,实现基线检测。采用双... 详细信息

为提升武器射击精度,设计激光散射特性的红外瞄准镜基线检测方法。通过固定瞄准镜并利用黑体发射红外激光,在镜子反射后形成红外平行光束,并在瞄准镜视场内生成靶标的像。通过调整瞄准镜分划中心与靶标像中心重合,实现基线检测。采用双向反射分布函数和基尔霍夫近似理论的驻留相位近似法,分析红外激光的散射特性及波长与散射角对成像精度的影响,从而提高基线检测的精度。实验证明:当入射波长在9.5μm左右时,射击目标粗糙度为8μm时,双站极化散射系数最低,在1.0左右;当散射角在29°左右时,射击目标粗糙度为8μm时,双站极化散射系数最低在0.146左右;校正后目标位置偏差平均为0.01 m。

关键词：激光散射特性红外瞄准镜基线检测反射分布函数基尔霍夫驻留相位近似法

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Effects of leaf age,elevation and light conditions on photosynthesis and leaf traits in saplings of two evergreen conifers,Abies veitchii and ***

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Journal of Plant Ecology 2020年第4期13卷 460-469页

作者： rina Suzuki Koichi Takahashi Department of Science Graduate School of Science and TechnologyShinshu UniversityAsahi 3-1-1Matsumoto 390-8621Japan Department of Biology Faculty of ScienceShinshu UniversityMatsumoto 390-8621Japan Department of mountain Ecosystem Institute for Mountain ScienceShinshu UniversityAsahi 3-1-1Matsumoto 390-8621Japan

Aims Subalpine coniferous species are distributed over a wide range of elevations in which they must contend with stressful conditions,such as high elevations and extended periods of *** evergreen coniferous species,Abies veitchii and Abies mariesii,dominate at low and high elevations,respectively,in the subalpine zone,central *** aim of this study is to examine the effects of leaf age,elevation and light conditions on photosynthetic rates through changes in morphological and physiological leaf traits in the two *** We here examined effects of leaf age,elevation and light conditions on photosynthesis,and leaf traits in *** and *** of the two conifers were sampled in the understory and canopy gaps at their lower(1600 m)and upper(2300 m)distribution *** Findings The two species showed similar responses to leaf age and different responses to elevation and light conditions in photosynthesis and leaf *** maximum photosynthetic rate of *** is correlated negatively with leaf mass per area(LmA)and non-structural carbohydrate(NSC)*** increased at high elevations in the two species,whereas NSC concentrations increased only in ***,the maximum photosynthetic rate of *** decreased at high ***,maximum photosynthetic rates correlate positively with nitrogen concentration in both *** the understory,leaf nitrogen concentrations decreased and increased in *** and ***,*** decreased and the chlorophyll-to-nitrogen ratio increased in understory conditions only for ***,suggesting it has a higher light-capture efficiency in dark conditions than does *** study concluded that *** has more shade-tolerant photosynthetic and leaf traits and its photosynthetic rate is less affected by elevation compared with ***,allowing *** to survive in the understory and to dominate at high elevations.

关键词： leaf chlorophyll leaf mass per area leaf nitrogen non-structural carbohydrate concentration stable carbon–isotope ratio

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Filling the Gaps to Solve the Extensin Puzzle

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molecular Plant 2018年第5期11卷 645-658页

作者： Eliana marzol Cecilia Borassi mauro Bringas Ana Sede Diana Rosa Rodriguez Garcia Luciana capece Jose m. Estevez Fundacion Instituto Leloir and Instituto de Investigaciones Bioquimicas de Buenos Aires (IIBBA-CO.NICEr) Avenida Patricias Argentinas 435 Buenos AiresCP C1405BWE Argentina Departamento de Quimica Inorganica Analitica y Quimica Fisica Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires (INQUIMAE-CONICET)Buenos Aires CP C1428EGA Argentina Instituto de Investigaciones en Ingenierfa Genetica y Biologia molecular Dr. Hector Torres (INGEBI-CONICET) Vuelta de Obligado 2490 Buenos Aires C1428ADNArgentina

Extensins （EXTs） are highly repetitive plant O-glycoproteins that require several post-translational modifi- cations （PTms） to become functional in plant cell walls. First, they are hydroxylated on contiguous proline residues; then they are O-glycosylated on hydroxyproline and serine. After secretion into the apoplast, O-glycosylated EXTs form a tridimensional network organized by inter- and intra-Tyr linkages. Recent studies have made significant progress in the identification of the enzymatic machinery required to process EXTs, which includes prolyl 4-hydroxylases, glycosyltransferases, papain-type cysteine endopeptidases, and peroxidases. EXTs are abundant in plant tissues and are particularly important in rapidly expanding root hairs and pollen tubes, which grow in a polar manner. Small changes in EXT PTms affect fastgrowing cells, although the molecular mechanisms underlying this regulation are unknown. In this review, we highlight recent advances in our understanding of EXT modifications throughout the secretory pathway, EXT assembly in cell walls, and possible sensing mechanisms involving the Catharanthus roseus cell surface sensor receptor-like kinases located at the interface between the apoplast and the cytoplasmic side of the plasma membrane.

关键词： Arabidopsis thaliana cysteine endopeptidases extensins glycosyltransferases peroxidases prolyl 4-hydroxylases

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Role of the miR-301a/Fra-2/GLIPR1 axis in lung cancer cisplatin resistance

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Signal Transduction and Targeted Therapy 2023年第2期8卷 377-380页

作者： Gian Luca Rampioni Vinciguerra m.rina capece Rosario Distefano Giovanni Nigita Andrea Vecchione Francesca Lovat Carlo m.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbusOH43210USA Department of Clinical and molecular medicine University of Rome‘Sapienza’Sant’Andrea HospitalRome00189Italy

Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related mortality ***-based chemotherapy represents the main treatment,despite about the 70%of tumors are intrinsically *** the mechanisms of platinum-re... 详细信息

关键词： lung cancer chemotherapy

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Statistical modelling for effect of mix-parameters on properties of high-flowing sand-concrete

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Journal of Central South University 2012年第10期19卷 2966-2975页

作者： T.BOUZIANI A.BENmOUNAH m.BDrina Rheology of Dispersed media Research Unit-MaterialsProcesses and Environment(UR/MPE) University of BoumerdesBoumerdes 35000Algeria Structures Rehabilitation and materials Laboratory(SREmL) University Ammar Telidji of LaghouatLaghouat 03000Algeria

The high-flowing sand-concrete （HFSC） containing natural sands as aggregate was carried out. The high fluidity and stability of HFSC can be achieved by tailoring the mix design parameters, such as fine to coarse sand ratio, dosage of additions, water to binder ratio and dosage of admixtures. mini-cone slump test, *** time test and viscosity model parameters were used to characterize the behaviour of HFSC in fresh state. The mechanical compressive strength in 28 d was also determined. A factorial design approach was used to establish models highlighting the effect of each mix-parameter on measured properties of HFSC. The derived models are valid for mixtures made with 0 to 0.3 of dune sand to total sand ratio, 82 to 418 kg/m3 of marble powder, 0.42 to 0.46 of water/binder ratio and 1.3% to 1.9% of superplasticizer high water-reducer. The results show that the derived models constitute very efficient means for understanding the influence of key mix-parameters on HFSC properties and are useful in selecting the optimum mix proportions, by simulating their impact on fluidity, stability and compressive strength.

关键词： high-flowing sand-concrete factorial design fluidity viscosity mix-design parameters

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萝卜硫素通过调节ALOX5/NF-κB信号通路调控巨噬细胞糖酵解抑制糖尿病肾病进展

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安徽医科大学学报 2024年第3期59卷 390-397页

作者：乌日娜丁海东常宏孙娜娜张磊内蒙古民族大学附属医院内分泌科通辽028000

目的探讨萝卜硫素(SFN)调节花生四烯酸5-脂氧合酶基因(arachidonic acid 5-lipoxygenase,ALOX5)/核因子kappa B(NF-κB)信号通路调节巨噬细胞糖酵解对糖尿病肾病(DN)进展的影响。方法生物信息学分析SFN治疗DN的靶基因。使用30 mmol/L高... 详细信息

目的探讨萝卜硫素(SFN)调节花生四烯酸5-脂氧合酶基因(arachidonic acid 5-lipoxygenase,ALOX5)/核因子kappa B(NF-κB)信号通路调节巨噬细胞糖酵解对糖尿病肾病(DN)进展的影响。方法生物信息学分析SFN治疗DN的靶基因。使用30 mmol/L高葡萄糖(HG)处理人近端肾小管上皮细胞系(HK-2细胞)诱导体外DN模型。将HK-2细胞分为如下组:正常糖(NG)组、HG组、HG+SFN(3 mmol/L)组、HG+ALOX5组、HG+SFN(3 mmol/L)+ALOX5组、HG处理的巨噬细胞+HK-2细胞组、HG+SFN(3 mmol/L)处理的巨噬细胞+HK-2细胞组、HG+ALOX5转染处理的巨噬细胞+HK-2细胞组、HG+SFN(3 mmol/L)+ALOX5转染处理的巨噬细胞+HK-2细胞组。CCK-8检测细胞活力,原位末端脱氧核苷酸转移酶标记(TUNEL)法检测细胞凋亡;葡萄糖和乳酸试剂盒检测各组细胞中葡萄糖和乳酸水平;Western blot检测各组细胞中ALOX5、NF-κB以及糖酵解相关蛋白己糖激酶-2(HK2)、丙酮酸激酶m2(PKm2)、葡萄糖转运蛋白1(GLUT1)的表达;使用链脲佐菌素(STZ)构建DN小鼠模型,DN小鼠给与SFN(0.5 mg/kg)治疗;检测小鼠各项生化指标,HE染色检测肾组织病理变化;Western blot检测小鼠肾脏巨噬细胞中糖酵解相关蛋白己糖激酶-2(HK2)、丙酮酸激酶m2(PKm2)、葡萄糖转运蛋白1(GLUT1)的表达。结果生物信息学分析结果显示ALOX5是SFN治疗DN的靶基因。与HG组相比,SFN处理增强HK-2细胞活力并抑制细胞凋亡(P<0.05);同时,SFN处理抑制HG诱导的巨噬细胞糖酵解相关蛋白的表达,减弱巨噬细胞介导的HK-2细胞损伤(P<0.05);Western blot结果表明SFN抑制ALOX5和NF-κB的表达(P<0.05);小鼠实验结果显示,SFN治疗改善DN小鼠肾功能和肾组织病理学改变,抑制肾组织中巨噬细胞糖酵解相关蛋白的表达(P<0.05)。结论SFN通过抑制ALOX5/NF-κB信号通路抑制巨噬细胞糖酵解从而改善DN进展。

关键词：萝卜硫素糖尿病肾病巨噬细胞糖酵解花生四烯酸5-脂氧合酶 NF-κB信号通路

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Stable carbon and oxygen isotopes of four planktonic foraminiferal species from core-top sediments of the Indonesian throughflow region and their significance

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Acta Oceanologica Sinica 2016年第10期35卷 63-75页

作者： ZHANG Peng ZURAIDA rina XU Jian YANG Ce State Key Laboratory of Continental Dynamics Northwest UniversityXi'an 710069China Institute of Cenozoic Geology and Environment Department of GeologyNorthwest UniversityXi'an 710069China marine Geology Institute Bandung 40174Indonesia

Horizontal and vertical distributions of δ^18 and δ^13 were investigated in shells of four planktonic foraminiferal species, Globigerinoides ruber, Globigerinoides sacculifer, Pulleniatina obliquiloculata and Neogloboquedrina dutertrei, from a total of 62 core-top sediment samples from the Indonesian throughflow region. Results were compared to modern hydrologic conditions in order to explore potential of proxies in reconstructing fluvial discharge and upper ocean water column characteristics in this region. Our results show that, in the makassar Strait, both of depleted δ^18 and δ^13 of these four species were linked to freshwater input. In the Bali Sea,however, depleted δ^18 and δ^13 for these species may be due to different reasons. Depleted δ^18 was a result of freshwater input and as well influenced by along-shore currents while depleted δ^13 was more likely due to the Java-Sumatra upwelling. Comparison of shell δ^18 records and hydrographic data of World Ocean Atlas 2005 suggests that G. ruber and G. sacculifer calcify within the mixed-layer, respectively at 0–50 m and 20–75 m water depth, and P. obliquiloculata and N. dutertrei within the upper thermocline, both at 75–125 m water depth. *** calcifies at slightly deeper water depth than P. obliquiloculata does. In general, δ^13 values of both *** and G. sacculifer are larger than those of P. obliquiloculata and N. dutertrei at all sites, possibly related to depth habitats of these species and vertical distribution of nutrients in the Indonesian throughflow region.

关键词： planktonic foraminiferal δ^18O and δ^13C calcification depth freshwater input Java-Sumatra upwelling Indonesian throughflow region

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Geochemical characteristics from tests of four modern planktonic foraminiferal species in the Indonesian Throughflow region and their implications

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Geoscience Frontiers 2019年第2期10卷 505-516页

作者： Peng Zhang rina Zuraida Yair Rosenthal Ann Holbourn Wolfgang Kuhnt Jian Xu Institute of Cenozoic Geology and Environment State Key Laboratory of Continental DynamicsDepartment of GeologyNorthwest University marine Geology Institute Department of marine and Coastal Sciences RutgersThe State University of New Jersey Institute of Geosciences Christian-Albrechts-University

Test geochemistry of planktonic foraminifera is an indispensable tool in reconstructing past ocean hydrological changes. It is essential to investigate region-specific implications of test geochemistry,although those established from other regions can be broadly applied. In this study, characteristics of6180 and mg/Ca from tests of four planktonic foraminiferal species, Globigerinoides ruber sensu stricto(s.s.), Globigerinoides sacculifer, Pulleniatina obliquiloculata and Neogloboquadrina dutertrei, from 60 coretop sediment samples retrieved from the Indonesian Throughflow(ITF) region were studied. These geochemical data were compared with modern hydrographic profiles in order to assess their relations and to investigate potential implications of test geochemical parameters in reconstructing past oceanographic change in the ITF region. Calcification depths of these four species were first estimated based on comparison between measured test δ180 and predicted calcite δ^(18)O that was calculated from modern temperature and salinity. The results indicate that G. ruber s.s. and G. sacculifer calcify within the mixedlayer at 0-50 m and 20-75 m, respectively, whereas P. obliquiloculata and N. dutertrei calcify within the thermocline at around 75 to 125 m. A combined study of excess mg/Ca(difference between measured and predicted mg/Ca) and salinity suggests that salinity exerts a negligible impact on test mg/Ca of these foraminiferal species in the ITF region. Comparison of test mg/Ca-derived temperatures with temperature profiles of the upper 200 m of the water column from the seas of the ITF region also indicate calcification depths of these species, which match well with the above estimations using test δ^(18)O. It further indicates that G. sacculifer may be more sensitive in reflecting changes in the depth of the mixedlayer, highlighting a potential use of mg/Ca temperature difference between G. ruber s.s. and G. sacculifer in reconstructing the depth of the mixed-lay

关键词： Test geochemistry multi-species Planktonic foraminifera Core-top sediments Indonesian Throughflow region

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